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Activation by CcpA-FDP of two key determinants of pneumococcal virulence, capsule production and choline utilization.

ABSTRACT: The kinetic behaviour of S. pneumoniae during vaccine production was studied using a dynamic systemic approach. Quantification of key intracellular glycolytic metabolites coupled to global transcriptomic analysis led to an improved knowledge of pneumococcal physiology. In controlled growth conditions, a direct correlation between the accumulation of key glycolytic intermediates and the expression of capsular polysaccharide genes (cps operon encoding the main pneumococcal antigen) was established. Interestingly, the same correlation was confirmed for the genes involved in the assimilation and the modification of choline, an indispensable nutritional requirement for both growth and virulence of S. pneumoniae. Such a correlation suggests a direct or indirect control of the expression of these genes by the global transcriptional regulator CcpA (catabolite control protein A) since putative cre sites upstream of the promoter were identified, even though the exact nature of this regulation remains to be confirmed. Preliminary results indicate that a ccpA mutation provokes a significant decrease in the expression of these genes. The global transcriptomic analysis coupled with motif research has revealed an extended CcpA regulon in S. pneumoniae including genes involved in diverse metabolic functions. Keywords: Capsular polysaccharide industrial production

ORGANISM(S): Streptococcus pneumoniae

PROVIDER: GSE9670 | GEO | 2008/12/01

SECONDARY ACCESSION(S): PRJNA103553

REPOSITORIES: GEO

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Activation by CcpA-FDP of two key determinants of pneumococcal virulence, capsule production and choline utilization.

Project description:The kinetic behaviour of S. pneumoniae during vaccine production was studied using a dynamic systemic approach. Quantification of key intracellular glycolytic metabolites coupled to global transcriptomic analysis led to an improved knowledge of pneumococcal physiology. In controlled growth conditions, a direct correlation between the accumulation of key glycolytic intermediates and the expression of capsular polysaccharide genes (cps operon encoding the main pneumococcal antigen) was established. Interestingly, the same correlation was confirmed for the genes involved in the assimilation and the modification of choline, an indispensable nutritional requirement for both growth and virulence of S. pneumoniae. Such a correlation suggests a direct or indirect control of the expression of these genes by the global transcriptional regulator CcpA (catabolite control protein A) since putative cre sites upstream of the promoter were identified, even though the exact nature of this regulation remains to be confirmed. Preliminary results indicate that a ccpA mutation provokes a significant decrease in the expression of these genes. The global transcriptomic analysis coupled with motif research has revealed an extended CcpA regulon in S. pneumoniae including genes involved in diverse metabolic functions. Keywords: Capsular polysaccharide industrial production One condition experiment examining the transcriptome between two growth phases of the same serotype (slide 1 to slide 4). Thus, cross analysis between the two serotypes during exponential growth was performed in order to complete the analysis

2010-05-15 | E-GEOD-9670 | biostudies-arrayexpress

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2011-03-01 | E-GEOD-27258 | biostudies-arrayexpress

An antibody to Streptococcus pneumoniae capsular polysaccharide enhances quorum sensing

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Glutamate dehydrogenase (GdhA) of S. pneumoniae is required for high temperature adaptation

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Project description:Invasive pneumococcal disease is preceded by asymptomatic colonization of the human nasopharynx by Streptococcus pneumoniae. Progression from colonization to invasion is a watershed in the host-pathogen interaction, and exposes the pneumococcus to markedly different microenvironments. This in turn, requires alterations in gene expression profile to adapt to the new niche. One apparent adaptive mechanism is reversible phase variation between “transparent” and “opaque” colony opacity phenotypes. Transparent phase variants colonize the nasopharynx more efficiently than opaque variants of the same strain, while opaque variants exhibit higher systemic virulence. Previous studies have reported quantitative differences in surface components such as the capsule, teichoic acid and certain surface proteins between the two phenotypes, but the underlying regulatory mechanism is not understood. In the present study, we found no differences in expression of key surface proteins between opaque and transparent variants of S. pneumoniae strain D39, but opaque cells produced five-fold more capsular polysaccharide. Subsequent microarray and real-time RT-PCR analysis showed no differences in capsule gene expression, but several genes involved in uridine monophosphate (UMP) biosynthesis were up-regulated in the opaque phenotype. This correlated with significant increases in the intracellular concentrations of both UMP and UDP-glucose, which are essential precursors for capsule biosynthesis. Our data suggest a novel mechanism for pneumococcal capsule regulation, in which rate-limiting precursor pathways are modulated rather than the capsule biosynthetic genes themselves. Keywords: Phase variants

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Serotyping of Streptococcus pneumoniae based on capsular genes polymorphisms

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2013-12-31 | E-GEOD-45865 | biostudies-arrayexpress

ccpA mutant compared to D39 wild-type in Streptococcus pneumoniae in CDM + galactose at transition-phase of growth (TS)

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